We studied 38 patients (24 men and 14 women) with an acquired ventricular septal defect during acute myocardial infraction (AMI) (rupture group) and compared clinical and necropsy findings in them with 50 patients who died during their first AMI without rupture (non-rupture group). The frequency of systemic hypertension (54%- vs.-52%), angina pectoris (28%-vs.-22%) and congestive heart failure (5-vs.-O%) before the fatal AMI was similar for both rupture and non-rupture groups. Mean heart weights for men (498 g-vs.-526 g) and women (397 g-vs.-432 g) with and without septal rupture also were insignificantly different. Whereas previous studies of fatal AMI cases have shown that 50% of cases of fatal AMI without rupture have left ventricular scars, only 4 (10%) of the rupture cases had a left ventricular scar before the infarct which ruptured. The rupture group had a significantly more frequent (P<0.01) posterior location of the infarcts (74%-vs.-40%), and therefore, a higher frequency of associated right ventricular infarcts 50%-vs.-18%). The number of 3 major (right, left anterior descending and left circumflex) epicardial coronary arteries narrowed at some point >75% in cross-sectional area by atherosclerotic plaque was the same in both groups. The percent of these 3 arteries totally occluded or nearly so (>95% in cross- sectional area) by plaque was significantly less (P<.001) in the rupture group compared to the non-rupture group (9 of 99 arteries (9%)-vs.-38 of 144 arteries (26%)). Analysis of each 5-mm long segment of these arteries in each group disclosed that the rupture group had significantly less narrowing than the non-rupture group.